1. Screens and tests for NPS Dr Paul Smith Consultant Clinical Scientist and Forensic Toxicologist paul.r.smith@uhl-tr.nhs.uk

2. Screens and tests for NPS Where we are now Scope for the future Potential for treatment / antidotes Opportunities in LLR

3. ‘£10 legal high made me parade naked through Tesco’

4. NPS Many different terms - legal highs, designer drugs, research chemicals Stimulant pills / powders Herbal smoking mixes Cheap Readily available Increasing prevalence Perception that legal = safe Many now illegal Cases of acute toxicity and death

6. EMCDDA Report 2015

7. Drug seizures

8. Immunoassay and GC-MS Uses commercial libraries of drugs and metabolites ~1000 drugs and metabolites Custom the library

9. Drug screen by LC-MS/MS NOT able to detect synthetic cannabinoids DRUG 1 4-MEC 2 6-MAM 3 Amphetamine 4 Benzoylecgonine 5 Buprenorphine 6 Cocaethylene 7 Cocaine 8 Codeine 9 Diazepam 10 Dihydrocodeine 11 EDDP 12 Gabapentin 13 MDA 14 MDEA 15 MDMA 16 Mephedrone (MCAT) 17 Methadone 18 Methamphetamine 19 Methylecgonine 20 Midazolam 21 Morphine 22 Nitrazepam 23 Norbuprenorphine 24 Nordiazepam 25 Oxazepam 26 Oxycodone 27 Oxymorphone 28 Pholcodine 29 Pregabalin 30 Temazepam 31 THC-COOH 32 Zopiclone

10. NPS screen by LC-MS/MS (post-mortem) 4-Fluoroamphetamine Paramethoxyamphetamine (PMA) Paramethoxymethamphetamine (PMMA) 4-Methylthioamphetamine (4-MTA) Methiopropamine Cathinone Cathine Methcathinone Flephedrone (4-fluoromethcathinone) Mephedrone (4-methylmethcathinone) 4-MEC (4-methylethcathinone) Methedrone (4-methoxymethcathinone) Benzedrone Methylone (beta-keto MDA) Ethylone (beta-keto MDMA) Butylone Clephedrone (4-chloromethcathinone) Benzylpiperazine (BZP) Trifluoromethylphenylpiperazine (TFMPP) 3-Chlorophenylpiperazine (MCPP) 2-Aminoindane Methylenedioxyaminoindane (MDAI) 5-Aminopropylindane (5API) Alpha-methyltryptamine (AMT) 5-Iodoaminoindane (5IAI) Methylenedioxypyrovalerone (MDPV) 5-APB / 6-APB Naphyrone Propylhexedrine Methoxetamine MBDB DOM DOET DOB Diclofensine Dimethocaine Desoxypipradol Ethylphenidate Etizolam Phenazepam NOT able to detect synthetic cannabinoids

11. Herbal products containing synthetic cannabinoids Black Mamba-type products are usually sold as herbal prep- arations containing inert herbal material (leaf etc.) saturated with synthetic cann- abinoids (SCs). The pure SC powder can also be bought online.

12. 1 st generation synthetic cannabinoids John W. Huffman, Ph.D, Over 400 JWH compounds “I always had a hunch that someday somebody would say: ‘Hey, let’s try smoking them.’ And lo and behold, that’s what happened.”

13. 2 nd generation synthetic cannabinoids

14. 3 rd generation synthetic cannabinoids

15. High resolution mass spectrometry Expensive equipment Specialist analysis Targeted and non- targeted screens High resolution as opposed to nominal mass (e.g. 271.5684 not 271) Full scan mode Capable of retrospective compound searching

16. Clinical cases CaseHistory Synthetic cannabinoid detectedOther drugs detected 1Extreme agitation in a psychiatric patient 5F-PB-22None 2 Prisoner found collapsed and fitting. History of black mamba use. 5F-AKB-48, 5F-PB-22, MDMB-CHMICA Mirtazapine, propofol, lignocaine, atracurium

17. Post mortem cases CaseHistory Synthetic cannabinoid detectedOther drugs detected 1Mixed drug intake5F-AKB-48 Diazepam, heroin, cocaine, mirtazapine, propranolol, phenytoin, olanzapine 2Collapse5F-AKB-48, 5F-PB-22None 3Agitation5F-AKB-48, 5F-PB-23Amphetamine, cocaine 4Agitation5F-AKB-48, MDMB-CHMICA Heroin, buprenorphine, promethazine, procyclidine, diazpeam, gabapentin, lorazepam 5Heroin and mixed drugs5F-AKB-48, 5F-PB-22Cocaine, heroin, amphetamine, 6Hanging5F-AKB-48, 5F-PB-23Ethanol 7Death in custody5F-AKB-48, MDMB-CHMICADiazepam, mirtazapine, amitriptyline, heroin, cocaine, thc 8Dead on sofa 5F-AKB-48, MDMB-CHMICA, THJ2201Morphine, lorazepam, 2 aminoindane 9DrowningAKB-48THC, promethazine 10Assault5F-AKB-48, 5F-PB-22THC, papracetamol 11UnknownJWH-018MDPV, ethanol 12Prison deathMDMB-CHMICADihydrocodeine 13Prison deathMDMB-CHMICAMirtazapine, alfentanil, prochlorperazine, lignocaine, atracurium, 14UnknownMDMB-CHMICAIbuprofen

18. Signs and symptoms CNS: agitation, tremor, anxiety, confusion, somnolence, syncope, hallucinations, changes in perception, acute psychosis, nystagmus, convulsions and coma. Cardiac: tachycardia, hypertension, chest pain, palpitations, ECG changes. Renal: acute kidney injury. Muscular: hypertonia, myoclonus, muscle jerking and myalgia. Other: cold extremities, dry mouth, dyspnoea, mydriasis, vomiting and hypokalaemia. Long term effect: no documented evidence

19. Treatment Supportive – NO ANTIDOTE Observe patient ECG U&Es, creatinine and CK Agitation and delirium - diazepam, haloperidol Convulsions - diazepam

20. Rapid drug test kit NPT devices do exist but are limited to specific compounds  JWH-018  JWH-073

21. Opportunities in LLR Funding required for equipment to increase understanding and recognition of NPS including synthetic cannabinoids Epidemiology studies Patient monitoring Potential to assist treatment decisions

22. K2/Spice